Method of formulating zinc oxide powder blends for balanced UVA/UVB attenuation

ABSTRACT

Disclosed is a composition that comprises an effective proportion of a first metal oxide powder having a primary particle size and a secondary particle size selected for the first metal oxide powder to attenuate UV A and an effective proportion of a second metal oxide powder having a secondary particle size selected for the second metal oxide powder to attenuate UVB. The mean secondary particle size of the first metal oxide powder is greater than the mean secondary particle size of the second metal oxide powder. In one embodiment, the first and the second metal oxide powders are both zinc oxide.

This application is a Divisional of U.S. Ser. No. 12/328,631, entitledMETHOD OF FORMULATING ZINC OXIDE POWDER BLENDS FOR BALANCED UVA/UVBATTENUATION, filed Dec. 4, 2008, which claims the benefit of U.S.Provisional Patent Application No. 60/992,711, entitled METHOD OFFORMULATING ZINC OXIDE POWDER BLENDS FOR BALANCED UVA/UVB ATTENUATION,filed on Dec. 5, 2007.

BACKGROUND

The present invention relates to novel zinc oxide powder blends, theirproduction and use and particularly, although not exclusively their usein cosmetics compositions. The invention includes methods of producingthe novel zinc oxide powder blends, the zinc oxide powder blendsproduced, and end product formulations incorporating the zinc oxidepowder blends. Without limitation the invention furthermore includescosmetic, pharmaceutical and sunscreen formulations, as well as cosmeticand sunscreen formulations all having UV-protective propertiesattributable to the incorporated zinc oxide blends. The ultraviolet(“UV” herein) region of the electromagnetic spectrum comprises threewavebands, designated UV A from 320 to 400 nm, UVB from 290 to 320 nmand UVC from 200 to 290 nm. The UV A bank can be further divided into UVAI from 320 to 340 nm and UV All from 340 to 400 nm. The visible portionof the spectrum is generally from about 400 to about 700 nm. Naturalsunlight is a potent source of UV radiation. UV radiation may composeabout 10 percent of the solar radiation reaching the earth's surface andis well recognized as the cause of serious biological damage to humansand other animals.

Awareness of the risks and prevalence of UV-induced skin cancer andconsciousness of the damaging cosmetic effects of ultraviolet radiationhave fostered recognition in recent years of the desirability ofavoiding or controlling the physiological damage wrought by harmfulultraviolet radiation, especially solar ultraviolet. UVC radiation isgenerally not problematic as little if any penetrates the atmosphere,but may be hazardous if artificial sources such as germicidal lamps orhigh or low pressure mercury arc lamps are employed.

In contrast to the UVC waveband which is filtered out, both UV A and UVBradiation reach the earth's surface from the sun and may be harmful.Longer wavelength ultraviolet rays in the UV A region, adjacent thevisible spectrum, which reportedly constitute 99% of the UV energyreaching the earth's surface, are considered to be the primary cause oftanning but to cause little burning. However, in the longer term UVArays are also believed responsible for skin aging, causing blotching,freckling, wrinkling and comparable problems. Ultraviolet radiation inthe shorter wavelength UVB region of from 290 to 320 nm, thoughcomprising only about 1% of the UV energy is considered more significantin causing burning. Accordingly, protection against UVB radiation hastraditionally been a primary target of sunscreen formulation. Morerecently, there has been a recognition of the desirability of alsoprotecting against UV A radiation to reduce long term skindeterioration.

More seriously, both the UVA and UVB wavebands may be implicated in skincancers including dangerous melanomas. Skin cancer is by far the mostprevalent of all cancers and the incidence in the US is increasingrapidly. For these and other reasons, consistent use of a topicalsunscreen is now strongly recommended and is widespread. In light ofthis need, the art contains many proposals for sunscreen agents andcompositions intended to provide protection from damaging ultravioletradiation.

Many and diverse UV-protective agents suitable for topical applicationin creams, sprays, lotions and the like is known and has been used insunscreens. However, most such agents are organic chemicals that areprone to photo degradation and may cross-react with other components ofdesirable topical formulations. Furthermore, being absorbable into theskin, organic sunscreens may irritate the skin or cause otherdermatological or allergenic problems. The art also contains proposalsfor broad spectrum UV protection.

For example, Deckner U.S. Pat. No. 5,783,174 describes sunscreencompositions intended to provide broad protection in both the UV A andUVB regions which compositions combine a UV A-absorbing dibenzoylmethanesunscreen with a UVB-absorbing benzylidene camphor sunscreen. Thiscomposition is intended to avoid problems of photochemical instabilityattributable, according to Deckner, to photoinduced interaction betweendibenzoylmethane and the widely used UVB absorber octylmethoxycinnamate.

A more recent demand for both higher SPF (“sun protection factor”)values and for broad-spectrum protection, has led manufacturers tocombine several different organic chemical ingredients, aggravatingpotential problems of photo-induced cross reactivity. To overcome thisproblem, Lapidot, et al. describe in U.S. Pat. No. 6,436,375 a methodfor microencapsulating at least one of two or more active sunscreeningredients which are photo-unstable when formulated together. Theactive ingredients can be selected for UVA and UVB activity and can beencapsulated in separate sol-gel microcapsules. A drawback of Lapidot etal.'s proposal is that even if problems of cross-reactivity and photodegradation can be overcome, which may or may not be the case, Lapidotet al.'s method still requires use of active organic sunscreen agentswhich may be harmful or irritating when absorbed. Furthermore, use ofsol-gel microcapsules adds complexity and expense and may be undesirablein some topical formulations. Such microcapsules may also raise issuesof dispersibility and compatibility with other ingredients of endproduct formulations.

There is accordingly a need for a UV-protective agent having broadspectrum activity against harmful solar radiation and which does notdepend upon organic chemicals. In light of the problems with organicmaterials, the suitability of inorganic materials may be considered.Several commercially useful inorganic UV-protective agents are known,notably titanium dioxide, zinc oxide and iron oxide. Iron oxides,however are usually colored or black and therefore have rather limiteduse in sunscreen applications. Also, they may not be approved for use assunscreens by regulatory authorities such as the US FDA.

Thus, considerable difficulties face a formulator or other workerseeking broad spectrum UV-protective agents that will be satisfactoryfor widespread commercial use in a full range of topical commercialproducts.

Elsom et al. (WO 90/11067) provide single-species metal oxide sunscreencompositions. Specifically provided are sunscreen compositionscontaining blends of titanium dioxide powders having a particle size of1-100 nm.

Likewise, Cowie et al. U.S. Pat. No. 4,927,464 also providessingle-species titanium dioxide compositions for absorbing UV radiation.Cowie et al. use acicular titanium dioxide wherein the length of thelongest dimension is 10-150 nm and the particles are coated with amixture of alumina and silica.

Iwaya U.S. Pat. No. 5,032,090 suggests use of a combination of titaniumdioxide and zinc oxide in anti-suntan cosmetic compositions to blockultraviolet rays in both the UVB and UV A regions. One drawback of thisapproach is that titanium dioxide may undesirably whiten or blue theskin in some formulations. Also the use of multiple metal oxides havingsignificant reactivity in many sunscreen systems may complicate theissues a formulator of compositions for human topical application mustaddress. Furthermore, although titanium dioxide is approved byregulatory agencies for many UV-protective applications, it is notapproved for use in combination with avobenzone, a popular organicsunscreen agent. In addition, titanium is not naturally present in humanand other organisms, and may therefore be an undesired ingredient forsome prospective users.

Iwaya U.S. Pat. No. 5,032,090 suggests use of a combination of titaniumdioxide and zinc oxide with a primary particle size great than 70 nm to300 run in anti-suntan cosmetic compositions to block ultraviolet raysin both the UVB and UV A regions. The primary particle size of the zincoxide claimed is too large to be effective in UVB.

Other formulations of the prior art use single-species zinc oxidecompositions for UV absorption. For example, Kobayashi Kose Co. JP60-231607 provides anti-suntan cosmetics containing 10-30% zinc oxidehaving a particle diameter of <100 nm.

Mitchell et al. U.S. Pat. No. 5,587,148 discloses sunscreen productsintended to absorb both UV A and UVB radiation while providing a clearappearance on the skin One embodiment of Mitchell et al.'s disclosureemploys micronized particles of zinc oxide having a size up to about 0.2μm and having what are purportedly reduced levels of toxic heavy metals,which are formulated with a liquid carrier into a colorless emulsion.According to Mitchell et al., this formulation “is capable of absorbinga substantial quantity, if not all, of the UV radiation to which theuser is exposed.” (Column 7, lines 15-17.) However, the Mitchell et al.specification provides little, if any, support for this conclusion.Other distinct embodiments proposed by Mitchell et al. include: use oflarge crystals of zinc oxide, measuring between about 1-100 microns indiameter; and use of transparent plastic spheres measuring between about0.01-100 microns in diameter which incorporate a UV-absorbing additive.

Cole et al. U.S. Pat. No. 5,340,567 provides sunscreen products intendedfor UV absorbance. Cole et al. provide mixed metal oxide compositionscontaining titanium dioxide having a particle size of less than about 35nm and zinc oxide having a particle size of less than about 50 nm. Themetal oxide particles used by Cole et al. are each of a singlesubstantially uniform size.

A disclosure by inventors herein Yun Shao and David Schlossman, “Effectof Particle Size on Performance of Physical Sunscreen formulas” PCIAconference, Shanghai, China R. P. (1999) (“Shao et al. 1999”hereinafter) and available, at the date of this application, describessome of the effects of size, surface treatment, dispersion vehicle,dispersant and other factors on the UV-protective performance ofinorganic sunscreens, notably titanium dioxide and zinc oxide. Shao etal. 1999 emphasize the importance of studying size reduction and therelationship between particle size and performance.

Shao et al. 1999 describe use of dispersions, or “pre-dispersions” oftitanium dioxide and zinc oxide, intended for formulation with otheringredients to provide useful end product. Shao et al. 1999 concluded atthat time that a high loading of solids in the dispersion were importantto size reduction and that other factors should also be considered,including pigment selection, surface treatment, vehicle and dispersant.Titanium dioxide is described as providing excellent protection againstUVB along with effective UV A protection at a larger size wherescattering may contribute significantly. However, such larger sizes maysacrifice some degree of SPF and transparency.

The protection afforded by zinc oxide is considered by Shao et al. 1999to vary inversely with particle size. Also, zinc oxide is described asproviding efficient UVA protection, often with a low SPF. One difficultythese findings present to the worker seeking to provide a broad-spectruminorganic UV-protective agent suitable for topical application, is thatdesired sizes of titanium dioxide particles may cause whitening on theskin, as may be understood from FIG. 5 of Shao 1999. (Nor does Shao etal. 1999 describe an adequate zinc oxide formulation.

Another disclosure of inventors, Yun Shao and David Schlossman herein,namely Discovering an Optimum Micropigment for High UV Shielding and LowSkin Whitening, 23rd IFSCC Congress Orlando 2004 (“Shao et al. 2004”hereinafter) describes studies on the UV attenuation of dispersions oftitanium dioxide having a primary particle size (“PPS”) as small as 15nm and of zinc oxide as small as 20 nm which studies include studies oftheir in vivo SPF efficacy. Shao et al. 2004 conclude that sizereduction of titanium dioxide and zinc oxide can remarkably improve theappearance of a sunscreen lotion and can improve the SPF in many cases.However, according to Shao et al. 2004, if the size of the titaniumdioxide particles is too small, the energy absorption may shift to UVCwavelengths, weakening the attenuation in the UV A and UVB wavebands.Shao et al. 2004 conclude that zinc oxide could provide an effective SPFat (secondary) particle sizes under 130 nm, but “at the cost of UV Aprotection”.

In this specification, “primary particle size” may be understood toreference an average or mean particle size of the metal oxide as drypowder while “particle size” sometimes referenced herein as “secondaryparticle size” for greater clarity, can be understood to reference theaverage mean particle size as it is determined in a dispersion of themetal oxide powder in a liquid.

As may be understood from Shao et al. 2004, secondary particle size mayoften be more important for ultraviolet protection than is the primaryparticle size, but the primary particle size of the dry powder is often,but not always, a principal factor in determining the secondary particlesize in a liquid dispersion. Some of the data described in Shao et al.2004 shows that secondary size does not always correlate with primarysize. The secondary particle size will usually be substantially greaterthan the primary particle size, possibly as much as five times greateror even more.

In vivo studies reported in boxes 7-9 of Shao et al. 2004 describeseveral properties of sunscreens employing the described titaniumdioxide and zinc oxide dispersions, including the SPF, the SPF per % ofactive ingredient and, in box 8, the PFA. “PFA” is a measure of theprotection afforded against UVA. Desirable values for PFA may be in therange of from about 4 to about 8. Referring to box 8, which addressesthe UV protection of zinc oxide dispersions, no PF As are reported forthe first three test samples, reading down Table 7, which are alldescribed as having relatively smaller (secondary) particles sizes,“PS(nm)”, of 110 nm or 130 nm. The last three samples are described ashaving larger (secondary) particles sizes of 228 nm, or greater, andyield PFAs which are in the target range.

Elsom et al. (WO 90/11067) provide sunscreen compositions which comprisea blend of different particle sizes of titanium dioxide. Preferredcompositions comprise 10 to 70% of titanium dioxide having a meanprimary particle size of about 15 nm and at least one further grade oftitanium dioxide having a mean primary particle size of between about 30nm and about 50 nm. One drawback of this approach is that titaniumdioxide may undesirably whiten or blue the skin in some formulations.The compositions are described as substantially transparent, however,because the refractive index of titanium dioxide is 2.6 they are likelyto be too whitening when the objective is to obtain an SPF 25 with a UVbalance of 4:1.

“Shao et al. 2004” is here described for the sake of completeness inelucidating the background of the present invention. However, it is tobe understood that no admission is made regarding the availability ofShao et al. 2004 as a reference in the United States or any other stateor region against the claims of the present application.

Thus notwithstanding the foregoing and other proposals in the art, thereis a need for improved UV-protective compositions having propertiessatisfying the various cosmetic and prophylactic needs of the end useras well as the requirements of a cosmetic formulator who must provideappealing, functional products which can be provided to consumers in asatisfactory and aesthetic condition.

In an earlier filed P.C.T. Patent Application No. PCT/US2006/041417,filed Oct. 23, 2006, we describe a composition which provides aninorganic UV-protective composition which can provide broad-spectrum UVprotection, while also being capable of being formulated into endproducts which have good transparency to visible light on the skin.

Generally, in accordance with the present invention, sunscreeningredients for cosmetics, sun tanning lotion, or the like in bothpowder and in liquid dispersion form are made from two differentsunscreen materials. Each of these two different sunscreen materials isselected for its characteristic of addressing either the UV A or the UVBcomponent of sunlight. In connection with this, it is noted that both ofthese components will attenuate UVA and UVB, but are, in the context ofthe multi-mode formulations of the present invention, more effective inaddressing either the UV A or the UVB component.

A desirable additional object of the invention is to provide aninorganic UV-protective composition capable of being formulated intodispersions which are non-whitening or induce little whitening at highsolids loadings. A still further useful object is to provide dispersionscontaining the inorganic UV-protective composition that avoid or inducelittle bluing on pigmented skin.

These and other objects can be achieved by one or more embodiments ofthe invention described herein.

In one aspect, the invention provides a zinc oxide powder compositionfor UV-protective use comprising a blend of:

a) an effective proportion of a first zinc oxide powder component havinga first particle size selected for the first zinc oxide powder componentto attenuate UVA; and

b) an effective proportion of a second zinc oxide powder componenthaving a second particle size selected for the second zinc oxide powdercomponent to attenuate UVB;

wherein the mean particle size of the first zinc oxide component isgreater than the mean particle size of the second zinc oxide component.

The relative proportions of the first and second zinc oxide componentscan be adjusted, or selected, to provide a desired balance of UV Aversus UVB protection. For example, the proportion by weight of thefirst component to the second component may be selected to be in therange of from about 1:2 to about 2:1. Some useful embodiments of theinvention employ a proportion by weight of the first component to thesecond component in the range of from about 1:1.4 to about 1:1.

In another aspect, the invention provides a UV-protective compositioncomprising an effective amount of a first zinc oxide particulatecomponent having a mean primary particle size in the range of from about30 to about 200 nm and an effective amount of a second zinc oxideparticulate component having a mean primary particle size in the rangeof from about 10 to about 30 nm. As indicated above, “primary particlesize” references the size of the dry, untreated powder.

In a further aspect, the invention provides an UV-protective compositioncomprising a dispersion in a liquid vehicle of an effective amount of afirst zinc oxide particulate component having a mean secondary particlesize greater than about 180 nm and an effective amount of a second zincoxide particulate component having a mean secondary particle size lessthan about 150 nm. As indicated above, the secondary particle sizereferences the size of the particles in the dispersion. Particle sizesreferenced herein are as determined by light scattering analysis, asdescribed hereinafter unless otherwise indicated explicitly or by thecontext.

Suitable dispersions may employ hydrocarbon or other fluids or oils orsilicone fluids as liquid vehicles, although aqueous vehicles may alsobe used. The dispersions are preferably solids-rich. Usefully, thesolids-rich zinc oxide dispersions may employ effective, usually small,proportions of chemical dispersing agents, or dispersants, as is knownto those skilled in the art. Also the zinc oxide particles may be coatedto enhance their dispersibility, as is also known in the art.

Alternatively, the formulator may incorporate the zinc oxide powderblend, in powder form, with other suitable ingredients to prepare afinal product. As a further alternative the zinc oxide powdercomponents, rather than being pre-blended may be separately added.

The two zinc oxide components can be supplied for incorporation into theUV-protective product as a particulate or powder blend or may beseparately added to one or more other ingredients to provide theUV-protective composition. Some process embodiments of the inventioninclude steps of blending the two or more dry zinc oxide powderingredients together and adding the blend to other ingredients. Pursuantto the invention it is believed that, in end product formulations, thefirst and larger zinc oxide component can provide useful UVA protectionand the second and smaller zinc oxide component can provide useful UVBprotection.

The first zinc oxide powder component can have a mean primary particlesize in the range of from about 50 to about 200 nm to provide UV Aprotection. In one embodiment of the invention the primary particle sizeof the first zinc oxide component is in the range of from about 60 toabout 100 nm.

The second zinc oxide powder component can have a mean primary particlesize in the range of from about 10 to about 30 nm to provide UVBprotection. In another embodiment of the invention the primary particlesize of the second zinc oxide component is about 20 nm.

Our earlier composition contemplated embodiments employing combinationsof the mean particle sizes of the first and second components, forexample one tranche of zinc oxide particles having a mean size in therange of about 50 to about 200 nm with another tranche of zinc oxideparticles having a mean size in the range of about 10 to about 30 nm,for particles of size of from about 60 to about 100 nm of the firstcomponent may be combined with particles of size of about 20 nm of thesecond component.

SUMMARY

In accordance with the present invention, it has been discovered thatwhen it is desired to fabricate blends of zinc oxide intended to provideprotection against both UV A and UVB radiation, effectively secondaryparticle size is of particular importance in achieving the desiredattenuation in the UV A range, while primary particle size is relativelyunimportant. Conversely, while secondary particle size is determinativein the case of attenuating UVB radiation, primary particle size isdesirably kept within certain ranges. Moreover, in accordance with thepresent invention, the distribution of particle sizes, and moreparticularly the content of oversize particles (for example, thosegreater than 280 nm) may be particularly important in preventingwhitening.

DETAILED DESCRIPTION

Some embodiments of the invention, and of making and using theinvention, as well as the best mode contemplated of carrying out theinvention, are described in detail below. The following more detaileddescription of the invention is intended to be read as a whole with thepreceding summary and background descriptions which may also includepertinent description of the invention, the scope of application of theinvention or of elements of the invention, as will be apparent to thoseskilled in the art, in light of this specification when read as a whole.

The present invention provides novel inorganic compositions ofparticulate, i.e. powdered, UV-protective ingredients that have broadspectrum activity and provide useful absorption and/or scattering inboth the UV A and UVB wavebands of the solar energy received at theearth's surface.

In one embodiment, the inventive compositions comprise first and secondzinc oxide powder components having particle sizes, or sizedistributions chosen to selectively attenuate, by absorption, scatteringor both absorption and scattering, the UV A and UVB wavebandsrespectively. For example, the one component may have relatively largerparticles to selectively absorb UV A and the other component may haverelatively smaller particles to selectively absorb UVB. Desirably, thetwo zinc oxide powder components can be formulated into compositions,such as dispersions, which are transparent when topically applied, forwhich purpose relatively small, submicron sized particles may beemployed.

UV-protective agents are agents which help or are intended to helpprotect organisms, especially humans and other susceptible animals, fromthe harmful effects of UV radiation, notably, without being so limited,solar radiation at the earth's surface. Typically, although notexclusively, such protection is obtained by topical application to theskin and other surfaces of compositions formulated with suitable,protective proportions of one or more UV-protective agents. It will beunderstood that compositions, including compositions described herein,which effectively protect human skin, may have other useful protectivefunctions e.g. in industrial coatings, plastics or other products.

“UVA” as used herein references the electromagnetic waveband from about320 nm to about 400 nm and “UVB” references the waveband from about 290nm to about 320 nm. The first zinc oxide component can be selected toprovide an attenuation peak in the UV A waveband, by absorption and/orscattering of the radiation which attenuation peak is useful inpreventing the harmful effects of UV A radiation. Comparably, the secondzinc oxide component can be selected to provide an attenuation peak inthe UVB waveband, by absorption and/or scattering of the radiation whichis useful in preventing the harmful effects of UVB radiation. Such acombination of components can provide effective broad-spectrumprotection against the UV components of atmospherically filtered solarradiation.

The inventive zinc oxide powder blends are to be understood to includenot only dry physical admixtures of the two defined zinc oxide powdercomponents but also other combination these two zinc oxide powdercomponents, for example dispersions of the two components in a liquidvehicle, which dispersions are formed by separate addition of theindividual zinc oxide powder components to the liquid vehicle. Endproducts, or intermediate products, which are themselves powder blends,or largely comprise powder blends, can also comprise the individuallyadded or blended zinc oxide components.

The invention provides compositions comprising relatively simpleingredient mixtures that are attractive to a cosmetics formulator to usein preparing formulations for topical application. Such formulations mayinclude, without limitation, sunscreen oils, creams, lotions and thelike, and other cosmetic, dermatologic, pharmaceutical or medicamentcompositions for topical or other use. One object fulfilled by theinvention is to provide beneficial UV-protective compositions whichavoid presenting new challenges or concerns to a cosmetics formulator.Another is to provide the formulator easy-to-use UV-protectivecompositions which can readily be incorporated not only in topicalsunscreen products to provide protection against acute exposure, butalso in other cosmetic products including, without limitation, productssuch as lipsticks and lip balms, makeups, nail polishes, hairtreatments, and so on, to provide everyday protection.

With these objectives in mind, the formulator may be faced with thedaunting challenge of assessing not only the individual safety andefficacy of a long list of ingredients under various conditions, butalso that of determining whether adverse cross-reactivity or otherinteractions may occur. For these understandable reasons, the formulatormay be reluctant to employ unfamiliar or untried ingredients orcombinations of ingredients that do not have a long history of safe andeffective use. The compositions of the present invention avoid theseproblems by providing novel UV-protective compositions which employactive ingredients that are known to be safe and effective and have along history of satisfactory use in a wide variety of cosmetic and otherformulations.

Proportion of Zinc Oxide in Solids Dispersions

The dual component zinc oxide materials of the invention can bedispersed into a suitable lipid, silicone or aqueous liquid vehicle inany desired proportion that will provide a smooth, homogenous dispersionand an effective proportion of zinc oxide for the intended purpose. Forexample, a proportion of from about 5 to about 90 percent by weight thezinc oxide material, based on the weight of the dispersion, can beemployed.

Some useful embodiments of the invention employ a zinc-oxide solidsloading, or proportion of at least about 20 percent, desirably at leastabout 30 percent, by weight, for example a proportion in a range of fromabout 20 to about 80 percent by weight. Lower proportions containing,for example, up to about 40 percent zinc oxide material, can be usefulfor direct topical application or other purposes. Higher proportionscontaining, for example, from about 50 to about 80 percent zinc oxidematerial, can provide useful “premix” solids-rich dispersions suitablefor use by cosmetic, pharmaceutical or other formulators for combiningwith other ingredients to provide useful consumer or other products, asdescribed herein.

For higher SPF values in the end product, and for other purposes, it maybe desirable to use a high proportion of zinc oxide solids in thedispersion, consistent with providing a stable, homogenous, dispersionthat has enough fluidity for processing. In other words, a high loadingof solids is generally desirable for product efficacy, but a loadingwhich is too high may cause processing difficulties or yield a poorquality product. Some useful embodiments of the invention employmore-or-less the highest loading of zinc oxide which can be obtained ina smooth dispersion that has sufficient fluidity for processing. Suchproducts may have a solids content in the range of from about 40 toabout 75 percent by weight of the dispersion.

A high proportion of solids in the liquid dispersion medium can bebeneficial to the objectives of the invention, as is described herein.For example, during milling of the dispersion, when milling is employed,a high proportion of solid particles can enhance attrition, causing morecollisions between particles and converting more of the input energy tosize reduction. In addition, a high proportion of solids provides theresultant dispersion with a high viscosity which may be advantageous,for example helping to control re-agglomeration.

Proportions of Zinc Oxide in End Products

Any proportion of zinc oxide powder or powder blend, may be employed inend product formulations that is effective for one or more of thepurposes described herein may be employed.

For example a desirable proportion of the two-component zinc oxidematerial of the invention may comprise from about 0.1 percent to about50 percent by weight of the end product. Desirably, the proportion isfrom about 1 to about 40 percent by weight. Higher proportions in eitherof these ranges, for example from about 2 to about 30 percent can beuseful in a variety of preparations that function primarily assunscreens and lower proportions, for example from about 0.1 to about 5percent by weight can be useful in preparations having other utilitieswhere a lower level of UV protection is considered useful, e.g. everydaycosmetics.

The invention includes embodiments of sunscreen or UV-protectivecompositions intended for topical application to skin, nail or haircomprising from about 2 to about 25 percent by weight zinc oxidematerial. One such embodiment, or group of embodiments, has a proportionof zinc oxide material of from about 5 to about 10 percent by weight ofthe end product. Another employs from about 10 to about 15 percent byweight of zinc oxide material.

Preparation of Dispersions and Formulation into End Products

Various methods can be employed to prepare the zinc oxide materials ofthe invention for delivery in a useful form to a cosmetics,pharmaceutical or other formulator, for formulation into UV-protectiveproducts useful to consumers or other end users.

For example, a specialist vendor, or other supplier may prepare a solidsrich dispersion of the zinc oxide powder blend in a liquid vehicle foruse by a formulator, or possibly for direct topical application. Theliquid vehicle in such solids-rich dispersions may comprise a suitableoil, a hydrocarbon, a silicone fluid, an aqueous medium or other usefuland suitable liquid medium.

The solids-rich zinc oxide dispersions in oil can for example beprepared by first mixing two or more dry powdered commercially availablezinc oxide powder components of desired size with the liquid vehicle, ina homogenizer or blender to break up agglomerates. Suitable zinc oxidematerials are available inter alia from Tayca Corp. and AdvancedNanotechnology Ltd., (Welshpool, Western Australia). Suitable oilsinclude, for example, isononyl isononanoate, octyl dodecyl neopentanoateand many other oils as are known in the cosmetics, pharmaceutical andother relevant arts. Other suitable liquids include aqueous vehicles andsilicone fluids.

The product of mixing, using a high sheer mixer or homogenizer, may besatisfactory, without milling.

However, if desired the dispersion product of the homogenizing orblending process can then be processed in a ball mill or the like toreduce agglomerates and aggregates into smaller particles, continuingmilling until a smooth, homogenous dispersion is obtained. The zincoxide powder components can be added as a powder blend or may be addedseparately to the liquid vehicle, while mixing, and/or agitating.

Surface Treatments or Coatings

Usefully, the zinc oxide powder materials may be surface treated toenhance the quality of the dispersion, increase the proportion of solidsthat can be successfully loaded into the liquid vehicle and thus helpprovide the end product with a small particle size. If desired, thesurface treatment can be selected according to the nature of theintended end product, some options for which are described below.

One or more surface treatment materials, for example a coating agent, isor are blended together with the zinc oxide powder, employing a smallquantity of solvent or dispersion vehicle, if needed for workability.This mixture is then heated, while blending or agitating, to a suitabletemperature, e.g. from about 110 to about 130 OC and for an appropriatetime e.g. from about 2 to about 4 hours or other suitable time period inthe range of from about 30 minutes to 24 hours to effect the surfacetreatment and any associated chemical reaction such as surface bonding,polymerization or cross-reaction. The treated zinc oxide material ismixed into a suitable cosmetic or other liquid vehicle and milled to afine particle size, for example to the finest size routinely obtainable.

Some suitable surface treatments are described in Shao et al. 1999 andinclude: use of metal soaps, titanates such as isopropyl titaniumtriisostearate or lecithin or the like to provide the treated zinc oxideparticles with lipophilic properties; use of various silicone materialssuch as methicone, dimethicone and multifunctional reactive silanes,e.g. triethoxy caprylylsilane to provide hydrophobic properties; and useof reactive fluorinated compounds such as fluoroalcohol phosphate toprovide both lipophobic and hydrophobic properties.

Other materials can be used for surface coating as known to thoseskilled in the art, or as becomes known as the art develops. Some suchuseful coatings, coated zinc oxide materials and formulations embodyingsame are disclosed in U.S. Patent Publications Nos.: 2005/0037041“Duplex coated color lake and other powders, their preparation andcosmetic and other uses”; U.S. 2004/0234613 “Hybrid coated cosmeticpowders and methods of making and using same”; and U.S. 2003/0161805“Organosilicon treated cosmetic powders, their production and use”; eachof which patent publications has at least one inventor in common withthe present application and are commonly owned with the presentapplication at the date hereof. The disclosure of each of said patentpublications is hereby incorporated herein by this specific referencethereto.

Dispersing Agent

With advantage a dispersing agent or dispersant can be employed in thedispersion to improve dispersion quality, for example PEG 10 dimethiconeor acrylates/ethylhexyl acrylate/dimethicone methylacrylate copolymer,or any other suitable dispersing agent as is known or becomes known inthe art, some examples of which include polymeric acid amines formed bycondensation of a polymeric acid with an amine, for example as describedin U.S. Pat. No. 4,349,389 at col. 5, 11.5-35, the disclosure of whichis hereby incorporated herein by reference thereto. The polymeric acidcan be a polyester derived from a suitable hydroxy organic acid, forexample hydroxystearic acid. The amine employed can be a loweralkylamine, di- or tri-lower alkylamine, or a polyamine for examplemethylamine, diethylamine, triethylamine, dimethylaminopropylamine,ethylenediame, triethylenetetramine, guanidine or a derivative thereof.Useful dispersing agents include SOLSPERSE (trademark), SOLSPERSE 9000,SOLSPERSE 3000 dispersing agents available from ICI Americas Inc.,Wilmington, Del. and the dispersing agents disclosed in U.S. Pat. Nos.4,349,389, 3,778,287 and 4,157,266. Many other suitable dispersingagents will be known to those skilled in the art, or will become knownas the art evolves.

For example, one useful embodiment of the invention employs apolyhydroxystearic acid as a dispersant for an oil, ester or hydrocarbonvehicle. Another embodiment employs castor oil phosphate as a dispersantfor such vehicles. For silicone-based dispersions, in silicone fluids, afurther embodiment of the invention employs a silicone polyether, forexample PEG-IO dimethicone as a dispersant.

Dispersion Analysis

With advantage, the viscosity and particle size of the resultantdispersion are then determined. Viscosity can be measured using aBrookfield RVT viscometer, or other suitable instrument, afterincubating samples at 25° c. for 24 hours. Particle size can be measuredby any suitable method. One useful particle size measurement employs alight scattering analyzer, for example a NICOMP 370 photo-correlationparticle analyzer. Secondary particle sizes described herein are to beunderstood to be as determined by such an instrument. Primary particlesizes are as determined and specified by a product supplier. If desired,the primary particle size can be determined or verified by such lightscattering analytic methods. As is known in the art, primary particlesize can be measured from a SEM (scanning electron micrograph) pictureor calculated from the specific surface area.

The formulator, or other party can mix the solids-rich zinc oxidedispersion, produced by the above or other suitable methods, with otheringredients to provide a desired cosmetic, pharmaceutical or otherproduct for topical application. Other suitable ingredients includecosmetic or pharmaceutical vehicles, pharmaceutically or cosmeticallyactive ingredients, excipients, additives, colorants, pigments,perfumes, water and the like, as is known, or becomes known, or apparentin the respective art. Blending, grinding, milling, mixing, heating,agitation, homogenization and other techniques may be employed, as willbe understood by these skilled in the art, to combine and process thevarious ingredients into useful end products.

If desired, and with advantage, in vivo tests can be performed on thesunscreen compositions produced, to determine in vivo values of SPF,optionally using a US FDA, or other suitable protocol. Such in vivotests can also be used to determine appearance, spreadability, aroma,and other aesthetic qualities, if desired.

In another embodiment of this aspect of the invention, the zinc oxidepowder blend, or the components thereof is, or are, admixed with otherpowder ingredients, for example pigments, fillers and so on, to providea powdered end product, for example make up.

Supplemental Organic Sunscreen Agent

The invention also provides a UV-protective composition comprising thedual-component zinc oxide material of the invention in combination withan organic sunscreen agent or agents. Usefully, the organic sunscreenagent can be selected to provide protection against UVB radiation,supplementing that provided by the inventive zinc oxide material. Anydesired organic UV-protective agent may be employed, as known, or thatbecomes known, to those skilled in the art, provided it is compatiblewith zinc oxide and other ingredients employed in the end product.

One example of a suitable organic UV-protective agent that may beemployed is octylmethoxy cinnamate (or 2-ethylhexyl p-methoxycinnamate),commonly abbreviated as “OMC”. Others include p-aminobenzoic acid,various benzophenones, oxybenzone, avobenzone, salicylates, variousother cinnamates and such organic sunscreen or UV-protective agents asare described in Gildenberg U.S. Pat. No. 6,217,852 and in the patentsand other publications referenced in Gildenberg. The disclosure of eachone of said patents and other publications is hereby incorporated hereinby this specific reference thereto.

Some examples of other organic UV-protective agents that can be employedinclude octyl salicylate, octocrylene, oxybenzone, 2-ethylhexylNsNdimethylaminobenzoate, p-aminobenzoic acid,2-phenyl-benzamidazole-5-sulfonic acid, homomenthyl salicylate,avobenzone (e.g., Parsol 1789), DEA pmethoxycirmamate, octylmethoxycinnamate, 4/4′-methoxy-tbutyldibenzoylmethane,4-isopropyldibenzoylmethane, 3-(4-methylbenzylidene) camphor,3-benzylidene camphor, 4-N,N-dimethylaminobenzoic acid ester with2,4-dihydroxybenzophenone, 4-NsN-dimethylaminobenzoic acid ester with2-hydroxy-4-(2-hydroxyethoxy)benzophenone, 4-N,N-dimethylaminobenzoicacid ester with 4-hydroxydibenzoyl-methane, 4-NsN-dimethylaminobenzoicacid ester with 4-(2-hydroxyethoxy)dibenzoylmethane,4-NsN-di(2-ethylhexyl)aminobenzoic acid ester with2,4-dihydroxybenzophenone, 4-N,N-di(2-ethylhexyl)aminobenzoic acid esterwith 4-hydroxydibenzoylmethane, 4-N,Ndi(2-ethylhexyl)aminobenzoic acidester with 4-(2-hydroxyethoxy)dibenzoylmethane,4-NsN-(2-ethylhexyl)methylaminobenzoic acid ester with2,4-dihydroxybenzophenone, 4-NsN-(2-hydroxyethoxy)benzophenone,4-N,N-(2-ethylhexyl)methylaminobenzoic acid ester with4-hydroxydibenzoylmethane, 4-N,N-(2-ethylhexyl)methylaminobenzoic acidester with 4-(2-hydroxyethoxy)dibenzoylmethane and mixtures of any twoor more of the foregoing organic UV-protective agents.

Any suitable proportion of the organic sunscreen agent can be employed.For example, the quantity, by weight may be somewhat less than thequantity of the inventive zinc oxide material employed, for example,from about 0.1 to about 2 parts organic agent, or agents, per part ofzinc oxide material referring to the combined weight of organic agentsif more than one is employed. Some useful embodiments of the inventionemploy from about 0.5 to about 1.2 parts organic agent, or agents, perpart of zinc oxide material, one embodiment of which employs about 0.8parts organic agent, or agents, per part of zinc oxide material.

Benefits

The novel dual-component zinc oxide powder materials of the presentinvention, compositions formulated from the dual zinc oxide powders andthe related methods described herein, provide a flexible, biocompatiblesolution to many ultraviolet protection problems. Cosmetic,dermatological, pharmaceutical, veterinary and other formulators areprovided with a novel means of affording both UV A and UVB protectionwith good transparency, biocompatibility and stability, in sunscreensand other products.

The invention provides a simple inorganic composition, or ingredientstherefor, useful embodiments of which have good broad-spectrumultraviolet efficacy, good SPF (sun protection factor) and PFA(protection factor UVA) which is easy to use, attractive to a cosmeticsformulator who must consider physical and chemical properties andinteractions of a multiplicity of ingredients. Useful embodiments of theinvention also provide good transparency enabling end products thatprovide good protection against sunlight, are non-allergenic andsuitable for extended daily wear and which are attractive to a widerange of users by virtue of their freedom from whitening or bluing.

The provision, by means of the invention, of broad spectrum UVprotection using zinc oxide alone, is chemically and biochemicallyadvantageous. The properties of zinc oxide are well understood. Thecomplications of using multiple, chemically diverse components can beavoided. If it is desired to employ an organic sunscreen agent forsupplemental UV A protection, the use of a single chemical entity forprimary broad spectrum protection limits potential interactivityproblems.

The various proportions of ingredients described herein are to beunderstood to be by weight based on the weight of the relevantcomposition comprising the ingredient in question, unless the contextindicates otherwise.

Products were prepared utilizing zinc oxide of various size, which weretreated, by methods known to one of skill in the art, with isopropyltitanium triisostearate or triethoxycaprylylsilane crosspolymer for easydispersion. The treated zinc oxide was dispersed in isononylisononanoate using a convention media mill, such as that made by Premieror Netzsch. Alternately, C12-C15 alkyl benzoate may be used as aneffective substitute for isononyl isononanoate. The mixture was thenmilled to the desired size in a manner known to one of skill in the art.

The resultant zinc oxide dispersions were used to make a water in oilsunscreen lotion, as more fully appears below. SPF (protection againstUVB) and PFA (protection against UVA) were tested in-vivo on threepanelists. To determine PFA, the PPD (persistent pigment darkening)method was used. Particle size in the dispersion was measured using aNICOMp C370 photo correlation size analyzer, Mean size of intensityweighted distribution is given below. Primary particle size of zincoxide is calculated from their BET specific surface area.

It is noted that the component referred to as providing UV A protectionalso provides some UVB protection and vice versa, and that suchreference is to the primary function.

Water in oil sunscreen formulas were prepared to investigate the effectof particle size on PF A, which, as noted above, measures effectivenessin protecting against UVA. Table 1 illustrates the composition, byweight percent, of Formula 1, results for which are reported in Table 2.

TABLE 1 Phase W/W % INCI NAME 1 3.00 Cetyl Dimethicone 7.50Cyclomethicone 6.00 Isononyl Isononanoate 0.50 Methyl GlucoseSesquistearate 2.00 Dioctyl Malate 5.00 Polyglyceryl-4 Isostearate (and)Cetyl Dimethicone Copolyol (and) Hexyl Laurate (ABIL®WEO9 available fromDeGussa) 2 21.33 Zinc Oxide dispersion in Isononyl Isononanoate 3 51.07Water 0.50 Sodium Chloride 2.50 PEG150/Decyl Alcohol/Smdi Copolymer(Aculyn 44 available from Rohm & Haas) 0.60 Phenoxyethanol (and)parabens (Phenonip® available from Nipa) 100

Formula 1 was prepared by mixing the Phase 1 ingredients, namely cetyldimethicone, cyclomethicone, isononyl isononanoate, methyl glucosesesquistearate, dioctyl malate, and polyglyceryl-4 isostearate, cetyldimethicone and hexyl laurate, using a propeller mixer. Mixing is doneuntil the mixture exhibits uniformity. Mixing may be carried out at roomtemperature or, optionally, heated to a temperature of 70-80° C. Thezinc oxide dispersion of Phase 2 is then added to the contents of thepropeller mixer to complete the “oil” phase.

The dispersion is made using a conventional method.

In a separate propeller mixer, the Phase 3 ingredients, water, sodiumchloride, peg-150/decyl alcohol/smdi copolymer, Phenonip®, are mixed ata temperature between 70° C. and 80° C., until the mixture is uniform,thus forming the water phase. Phase 3 is then slowly poured into themixture of Phase 1 and Phase 2, and mixing is continued until uniformityis achieved. Overmixing is not a problem and mixing may thus becontinued until uniformity stabilizes. The resulting mixture is thenhomogenized at 3000 rpm in a conventional homogenizer for 10 minutes at70-80° C. The finished mixture is then allowed to cool to roomtemperature.

TABLE 2 Formula 1 2 3 4 5 PPS (nm) −100 15-35 60 20 20 PS in disp. 263228 163 166 130 (nm) Active (%) 16 14.97 14.97 14.97 13.80 SPF 12.6 1420.4 17.4 25.4 SPF/Active % 0.79 0.93 1.36 1.16 1.84 PFA 5.83 7.50 7.588.17 4.75 PFA/Active % 0.46 0.50 0.51 0.54 0.34 SPF/PFA 2.2/1 1.9/12.7/1 2.1/1 5.4/1

In Table 2, the size of primary particles in manometers is reported as“PPS”. “PS” refers to secondary particle size, or the particle size ofaggregates in the dispersion. “Active (%)” refers to the percentage byweight of the active ingredient, namely the zinc oxide. “PF A” refers toUV A protection.

Formulae 2-5 were prepared in the same manner as a Formula 1, except forthe use of zinc oxide having the primary particle size and the secondaryparticle size indicated in Table 2, and except for the adjustment of theamount of isononyl isononanoate. More particularly, the adjustment ofthe amount of isononyl isononanoate was made to compensate for thechange in percent actives. For example, in Formula 2, the amount of zincoxide is reduced by 1.03 parts. Accordingly, the amount of isononylisononanoate was increased by 1.03 parts to result in a product havingthe reported percent of active material.

From the above, it can be concluded that the smaller the reported sizein dispersion, the more effective ZnO is in protecting against UVB. At asize of 130 nm or smaller, ZnO can be a very effective UVB sunscreen. Italso appears that it is largely the aggregate size, rather than theprimary particle size, that has a decisive influence on SPF score.

For UVA protection, there is an optimal size range of secondary particlesizes, which was found to include 160-230 nm and is believed to rangebetween 150 nm and 250 nm. When size is larger, the ZnO is not fullyutilized for absorption, as particles located on the outside of thelarge aggregate shield inside particles from radiation. When the size issmaller, the effective absorption range narrows.

It also appears from the above results that optimal sizes for UVA andUVB attenuation for zinc oxide are different. In order to formulate fora balanced UV protection, a combination of different sizes appearsdesirable. Thus, a zinc oxide dispersion with a secondary particle sizeof 130 nm will provide excellent UVB protection. Zinc oxide dispersionswith much larger size particles were used to provide UV A protection, ina number of formulations tested, as detailed in Table 3.

TABLE 3 Formula 6 7 8 ZnO for UVB PPS (nm)  20 Attenuation PS (nm) 130 %12 10 10 ZnO for UVA PPS (nm) 60 15-35 Attenuation PS (nm) 250 193 220 —10 10 12 SPF 31.4 30 30.7 PFA 11.6 8.7 9.3 FDA rating High High High

The water in oil sunscreen formulations designated Formulae 6-8 wereprepared using the method described above in connection with thepreparation of Formula 1. Again, to the extent that the percentage ofzinc oxide has been reduced from 16%, the amount of isononylisononanoate has been increased by the same weight. In Formulae 6-8, theUVB attenuating zinc oxide with a primary particle size of 20 nm wasobtained from a dispersion sold by Kobo under its catalog numberTNP50ZSI. In Formula 6, the UV A attenuating zinc oxide was obtained byusing a dispersion sold by Kobo under its catalog number TNC65SZ5. InFormula 7, the UV A attenuating zinc oxide was obtained by using adispersion sold by Kobo under its catalog number TNP50FZS. In Formula 8,the UV A attenuating zinc oxide was obtained by using a dispersion soldby Kobo under its catalog number INH73MZ.

All of the above formulae have SPF of 30 or higher and an excellent PA,indicating excellent broad-spectrum protection. Formula 6 used sizes attwo extremes, and the results met the standard of 3/1 SPF/PFA ratio.Accordingly it is believed that high balanced UV protection can beachieved with a blend of ZnO with sizes at two extremes.

The UV attention of zinc oxide depends more on its aggregate size thanthe primary size. At very small size, it can be an effective SPFprovider. When the particle size is in the range of about 165-220 nm, itis very effective against UVA.

In accordance with the invention, it has been learned that the componentof zinc oxide useful for attenuating UVA radiation may be fabricatedwith zinc oxide particles having a mean primary particle size less than120 nm. The dispersion is made to result in a secondary mean particlesize of 150 to 250 nm, preferably 160 to 240 nm. However, secondary meanparticle sizes of 140 to 260 nm will work well and functional resultscan be obtained with secondary mean particle sizes of 120-280 nm.

It is noted that the above specifications apply to zinc oxideparticulates currently available on the market. Other materials havingdifferent, for example, more narrow, particle size distributions mayenable equivalency outside these ranges.

Secondary particle sizes for particles intended to protect against UV Aradiation need only be less than 120 nm in size, as such smallerparticles may be aggregated during the dispersion manufacturing processto be in the above specified ranges.

Dispersions incorporating mixtures of zinc oxide particles meant toattenuate UV A radiation should be formulated to have 30% or more of theabove particles for an SPF of 30 and a ratio of SPF to PFA of 3:1. Forsimilar results finished products should have secondary particle sizezinc oxide concentrations as specified above in the range of 8% byweight.

However, dispersions having 10% or greater UVA attenuating zincparticles may be usefully employed. Likewise, finished products having2% or more UV A attenuating zinc oxide with secondary particles sizes asspecified above will also find useful employment.

The component of zinc oxide useful for attenuating UVB radiation may befabricated with zinc oxide particles having a mean primary particle sizeless than 55 nm, preferably less than 35 nm. However primary particlesizes less than 75 nm will yield useful results.

Secondary particle sizes are preferably less than 140 nm, and morepreferably less than 130 nm, although mean particle sizes in the 50-150nm range will provide functional results.

It is noted again that the above specifications apply to zinc oxideparticulates currently available on the market. Other materials havingdifferent, for example, more narrow, particle size distributions mayenable equivalency outside these ranges.

Dispersions incorporating mixtures of zinc oxide particles should beformulated to have 30% or more of the above particles meant to attenuateUVB radiation for an SPF of 30 and a ratio of SPF to PFA of 3:1. Forsimilar results finished products should have secondary particle sizezinc oxide concentrations as specified above in the range of 8% byweight.

However, dispersions having 10% or greater UVB attenuating zincparticles may be usefully employed. Likewise, finished products having2% or more UVB attenuating zinc oxide with secondary particles sizes asspecified above will also find useful employment.

As alluded to above, the mean secondary particle sizes are determined bymeasuring using a photon correlation particle size analyzer, also knownas a dynamic light scattering particle size analyzer, such as that madeby Particle Size Systems of Santa Barbara, Calif.

With respect to primary particle size measurements, the same arespecified using sizes determined using the BET surface area calculationmethod.

Dispersions may be prepared by incorporating zinc oxide particles intosuitable carriers and milling using conventional techniques of UV Aattenuating zinc oxide has the desired secondary particle size to make afirst dispersion. The dispersions or compositions incorporating suchdispersions may also include at least one biocompatible excipient (e.g.,buffer (neutralizer or pH adjusters), emulsifier, surfactant, diluent,adjuvant, preservative, and/or electrolyte).

The UVB attenuation particles are then incorporated into a carrier andmilled until the desired secondary particle size is obtained to make asecond dispersion.

The first and second dispersions are then combined.

The entire disclosure of each and every United States patent and patentapplication, each foreign and international patent publication, of eachother publication and of each unpublished patent application that isreferenced in this specification or elsewhere in this patentapplication, is hereby incorporated herein, in its entirety, by therespective specific reference that has been made thereto.

While illustrative embodiments have been described above, it is, ofcourse, understood that various modifications will be apparent to thoseof ordinary skill in the art. Many such modifications are contemplatedas being within the spirit or scope of the appended claims.

What is claimed is:
 1. A method of formulating a composition containinga Zinc oxide powder comprising: mixing a first Zinc oxide powder and asecond Zinc oxide powder in an aqueous or non-aqueous medium to preparea dispersion of the first and the second Zinc oxide powders; wherein thefirst Zinc oxide powder and the second Zinc oxide powder both formaggregates in the dispersion and a mean secondary particle size of thefirst Zinc oxide powder is greater than a mean secondary particle sizeof the second Zinc metal oxide powder wherein the mean secondaryparticle size for the first Zinc oxide is about 150 nm to about 260 nmand the mean secondary particle size for the second Zinc oxide is about130 nm or smaller.
 2. The method of claim 1 further comprising millingthe dispersion.
 3. The method of claim 1 wherein the aqueous ornon-aqueous medium is selected from the group consisting of an oil, ahydrocarbon, a silicone, and water.
 4. The method of claim 1 furthercomprising mixing the dispersion with a biocompatible excipient.
 5. Themethod of claim 1 wherein the Zinc oxide is about 5% to about 90% byweight of the dispersion.
 6. A method to make a sunscreen compositioncomprising: mixing a first Zinc oxide powder and a second Zinc oxidepowder in an aqueous or non-aqueous medium to prepare a dispersion ofthe first and the second Zinc oxide powders; wherein the first Zincoxide powder and the second Zinc oxide powder both form aggregates inthe dispersion and a mean secondary particle size of the first Zincoxide powder is greater than a mean secondary particle size of thesecond Zinc oxide powder, powder wherein the mean secondary particlesize for the first Zinc oxide is about 150 nm to about 260 nm and themean secondary particle size for the second Zinc oxide is about 130 nmor smaller.
 7. The method of claim 6 wherein the sunscreen compositionhas a Sun Protection Factor (SPF) of at least about
 25. 8. The method ofclaim 7 wherein the SPF is about
 30. 9. The method of claim 7 whereinthe sunscreen composition has a Protection Factor UVA (PFA) of at leastabout
 8. 10. A method to make a cosmetic composition comprising: mixinga first Zinc oxide powder and a second Zinc oxide powder in an aqueousor non-aqueous medium to prepare a dispersion of the first and thesecond Zinc oxide powders; wherein the first Zinc oxide powder and thesecond Zinc oxide powder both form aggregates in the dispersion and amean secondary particle size of the first Zinc oxide powder is greaterthan a mean secondary particle size of the second Zinc oxide powderwherein the mean secondary particle size for the first Zinc oxide isabout 150 nm to about 260 nm and the mean secondary particle size forthe second Zinc oxide is about 130 nm or smaller.
 11. The methodaccording to claim 1, wherein the composition further comprisescomprising organic UV absorbers, sunscreen agents or UV protectiveagents.